FDA Prioritizes Review of Sarclisa for Untreatable Newly Diagnosed Multiple Myeloma

The U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for Sarclisa (isatuximab) combined with bortezomib, lenalidomide, and dexamethasone (VRd), aiming to treat newly diagnosed multiple myeloma (NDMM) patients ineligible for transplants. The FDA has granted this application Priority Review, with an expected decision date of September 27, 2024. If approved, Sarclisa would become the first anti-CD38 therapy to be combined with standard VRd treatment for this patient group, marking its third indication in multiple myeloma. Similar regulatory submissions are also being reviewed in the European Union (EU).

The Chief Medical Officer and Global Head of Development at Sanofi, Dr. Dietmar Berger, highlighted the significant unmet need for new frontline therapies in multiple myeloma, especially for patients who are not eligible for transplants. He emphasized that the Priority Review status reinforces confidence in Sarclisa as a potentially best-in-class treatment, indicating a vital step toward addressing this challenging cancer.

The sBLA and the EU submission are based on the promising results from the IMROZ phase 3 clinical study. This study, conducted in December 2023, achieved its primary goal during an interim analysis, showcasing a statistically significant improvement in progression-free survival (PFS) for patients treated with Sarclisa in combination with VRd, compared to those treated with VRd alone. The safety and tolerability of Sarclisa were consistent with its established profile.

The IMROZ study is the fourth phase 3 trial to demonstrate the superiority of Sarclisa combinations in treating newly diagnosed multiple myeloma, reinforcing its potential as a leading treatment. The results of this study will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) Annual Congress.

Priority Review is a designation granted to therapies that could significantly improve the treatment of serious conditions. The global, randomized, multi-center, open-label IMROZ study enrolled 446 newly diagnosed, transplant-ineligible multiple myeloma patients across 21 countries and 104 centers. Sarclisa was administered intravenously at 10 mg/kg, initially weekly for five weeks, then bi-weekly from cycle 2 to 4, and subsequently in varying frequencies in combination with VRd until disease progression or adverse safety profiles emerged.

The study’s primary endpoint was progression-free survival. Key secondary endpoints included complete response rate, minimal residual disease (MRD) negativity rate, overall survival, duration of response, and overall response rate, among others. The investigational use of Sarclisa with VRd is still under clinical development, with its safety and efficacy not fully evaluated by regulatory authorities.

Sarclisa is a monoclonal antibody targeting a specific epitope on the CD38 receptor on multiple myeloma cells, inducing antitumor activity through mechanisms like programmed cell death and immunomodulatory activities. Already approved in over 50 countries, including the U.S. and EU, for treating relapsed refractory multiple myeloma (RRMM) in combination with other drugs, Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies for various multiple myeloma treatments and is also being investigated for other hematologic malignancies.

Multiple myeloma is the second most prevalent hematologic malignancy with over 180,000 new cases diagnosed globally each year. Despite advancements in treatment, it remains an incurable disease with a five-year survival rate of approximately 52% for newly diagnosed patients, often leading to relapse or refractory disease.